Genetic ancestry associated with obesity and diabetes risks in a Mexican-American population from Houston, Texas. H. Hu, C. D. Huff, Y. Yamamura, X. Wu, S. S. Strom Epidemiology, UT MD Anderson Cancer Center, Houston, TX.

   The Mexican-American population is an admixed ethnic group with varying proportions of Native American, European and African ancestries. African Americans and Native Americans have higher incidence rates of obesity and diabetes compared to Europeans due to a combination of environment and genetic factors. However, the relative contribution of genetic ancestry is not clear. In this study, we focus on a well-defined Mexican-American population in Houston, Texas, which is a socioeconomically homogeneous but genetically diverse population, making it ideal for studying the genetic epidemiology of inherited diseases. We genotyped 96 ancestry informative markers in 4,817 individuals, and used ADMIXTURE to estimate the composition of genetic ancestry in each individual. The mean proportions of Native American, European and African ancestries among all individuals were 62.9%0.3%, 30.7%0.3%, and 6.4%0.1%, respectively. Multivariate logistic regression models were constructed. In females, we found that African ancestry was significantly associated with obesity after controlling for confounders. Specifically, a 5% increase in African ancestry corresponded to a 12% increased risk of grade 2 obesity (BMI between 35 and 40; p=0.037) and an 18% increased risk of grade 3 obesity (BMI>40; p=0.006). In contrast, Native American ancestry was associated with increased risk of being overweight (BMI between 25 and 30; p=0.031), while its association with grade 1 obesity was positive but non-significant. In males, we did not observe any significant association between genetic ancestry and obesity (p>0.1). Our preliminary analysis on the risk of diabetes identified a positive and significant correlation between Native American ancestry and diabetes risk in females, after controlling for age, socioeconomic status, physical activity, smoking, alcohol consumption, and BMI (p=0.018). We estimated that 10% increase in Native American ancestry increases the risk of diabetes by 0.7%. We found no association between African ancestry and diabetes risk. In conclusion, our study suggests that among the Mexican-African population, African ancestry is a strong risk factor for obesity, and Native American ancestry is a modest risk factor for overweight and diabetes. Interestingly, both associations were only observed in females, indicating that the increased risk could be related to the lifestyle characteristic of females in this population.

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